title: Delivery of macromolecules across oral mucosa from polymeric hydrogels is enhanced by electrophoresis (iontophoresis).
abstract: OBJECTIVE
  To develop polymeric hydrogel delivery systems for iontophorseis transfer of large molecules across buccal (porcine) mucosa.
  
  
  METHODS
  Three hydrogels (PVA, HPMC and PVA/HPMC) were prepared as stable gels (7 mm diameter/1.5 mm thick). Quantitative (8 and 36 h) assessment of porcine buccal mucosa and the three hydrogel delivery systems, using a diffusion cell in vitro model, was carried out by UV/vis spectroscopy with three model agents (3 and 10 kDa dextrans and 12 kDa parvalbumin). Passive and iontophoresis parameters were obtained. Experimental and theoretical data were compared.
  
  
  RESULTS
  Iontophoresis (30 min, 1-8 h) significantly enhanced the delivery of all model agents across four single systems (hydrogels and buccal mucosa) and three sandwich systems (hydrogels on top of buccal mucosa), as confirmed by time lag factor/enhancement ratio (TLF/ER) data. The diffusion coefficients of model agents across buccal mucosa (×10(-13) m(2) s(-1)) were ~100 times lower than across single hydrogels (2.97-4.80×10(-11) m(2) s(-1)). Solubility values of all agents across hydrogels were similar, but lower across buccal mucosa. Permeability of parvalbumin was highest across PVA, and for both dextrans across PVA/HPMC. In sandwich systems TLFs were similar for all hydrogels, but significantly lower, and ERs significantly higher, than tissue alone. Experimental and theoretical TLF data were in reasonable agreement.
  
  
  CONCLUSIONS
  The in vitro data show that iontophoresis enhanced the delivery of large molecules across polymeric hydrogel systems and buccal mucosa. This creates the opportunity of new approaches to drug delivery and opens pathways to further research for delivering therapeutic agents topically and systemically.
authors.affiliation: Oral Growth and Development, Dental Physical Sciences, Barts and the London School of Medicine and Dentistry, Queen Mary, University of London, London, United Kingdom. Electronic address: M.Patel@qmul.ac.uk.
authors.forename: Mangala P
authors.initials: MP
authors.lastname: Patel
authors.forename: Svetla T
authors.initials: ST
authors.lastname: Churchman
authors.forename: Alan T
authors.initials: AT
authors.lastname: Cruchley
authors.forename: Michael
authors.initials: M
authors.lastname: Braden
authors.forename: David M
authors.initials: DM
authors.lastname: Williams
mesh_terms: D000818:Animals; D004337:Drug Carriers; D020100:Hydrogels; D007478:Iontophoresis; D009061:Mouth Mucosa / Q000378:metabolism*; D011108:Polymers; D013552:Swine
chemical_list: D004337:Drug Carriers; D020100:Hydrogels; D011108:Polymers
keywords: Buccal mucosa; Dextran; Diffusion; Drug delivery; Enhanced permeation; Ionotophoresis; Parvalbumin; Permeation cell; Polymeric hydrogels; Theoretical aspects